BioMed Research International / 2019 / Article / Tab 1

Review Article

Biologics in the Treatment of Lupus Erythematosus: A Critical Literature Review

Table 1

Biologics in systemic lupus erythematosus.

AgentMechanism of actionMolecular targetClinical phase of completed clinical trialsClinical phase of ongoing clinical trialsMajor outcomes/Safety profileFuture prospects

BelimumabBLyS inhibitionBLyS (soluble)III [19, 20, 27]III, IVSignificantly higher SRI-4 response at week 52 in three major phase III clinical trials than placebo. Positive impact on immunological parameters.++
(approved in EU and US as for the use in non-renal SLE as add-on therapy)

TabalumabBLyS/APRIL inhibitionBLyS (soluble and membrane-bound)III [38, 39]-No significant benefits over placebo (SRI-5). Slightly higher proportion of responders compared to placebo in post hoc analysis using SRI-4.+/-
(studies were discontinued)

Blisibimod
BLyS/APRIL inhibitionBLyS (soluble and membrane-bound)III [43]-No significant clinical benefits. Beneficial biological effects.+/-

AtaciceptBLyS/APRIL inhibitionBLyS, APRILIIb [49]-Slightly better SRI-4 response in patients with low-to-moderate disease activity compared to placebo. High risk of infective complications.+/-

Abetimus sodium
B cell tolerance inductionAnti-dsDNA antibody-producing B cells/circulating anti-dsDNA antibodiesII/II, III [53, 54]-Promising results in phase II/III clinical trials. No efficacy in phase III clinical trials.+/-

Rituximab
B cell depletionCD20III [62, 63]II, III
(including LN)
Primary end points in clinical trials not reached. Large number of reports and recommendations confirming its efficacy in certain subsets of patients.+

Ocrelizumab
B cell depletionCD20III [85]-Clinical trials prematurely terminated due to increased risk of adverse events.-

Ofatumumab
B cell depletionCD20Case series [87, 88]-Reduction of disease activity and anti-dsDNA antibody titres. Normalization of C3 complement component.+

Obinutuzumab
B cell depletionCD20Preclinical studies [93]II (LN)B cell depletion at least 2-fold more efficient than rituximab.+

Epratuzumab
B cell signaling modulationCD22III [102]-Lack of clinical efficacy. Favorable safety profile.-

Rontalizumab
Type I interferon inhibitionIFNαII [119]-No general superiority over placebo. Significant benefit in low IFN signature group.+/-

SifalimumabType I interferon inhibitionIFNαIIb [122]-Better SRI-4 response in high IFN signature group.+
(studies were discontinued)

Anifrolumab
Type I interferon inhibitionIFNAR1IIb [126]III (several trials including LN)Better SRI-4 response in high IFN signature group.+

Tocilizumab
Cytokine inhibitionIL-6 receptorI [140]-Improvement in clinical parameters. Reduction of anti-dsDNA antibody titers.+

Sirukumab
Cytokine inhibitionIL-6II (proof-of-concept) [142]-Lack of clinical efficacy. Frequent serious adverse events.-

Eculizumab
Complement blockadeMonoclonal antibody against complement component C5I [149]-Short-lasting biological efficacy was noted only for higher doses.-

Ruplizumab/
Toralizumab
T cell costimulation blockadeCD40LOpen label/
I [151, 152]
-Clinical trials were terminated due to thromboembolic complications.-

Dapirolizumab
T cell costimulation blockadeCD40-CD40LIb [153]IIIDisease activity reduction (SRI-4, BICLA).+

Abatacept
T cell costimulation blockadeCD28/CTLA4-CD80/CD86IIb, II/III [159, 160]III (including LN)No significant clinical benefits. Most beneficial in patients who had polyarthritis as the primary manifestation. Safe and well tolerated.+

APRIL: a proliferation-inducing ligand; BICLA: BILAG-based Combined Lupus Assessment; BLyS: B lymphocyte stimulator; CD40L: CD40 ligand; CTLA4: cytotoxic T lymphocyte associated protein 4; IFNα: interferon alpha; IFNAR1: interferon alpha receptor 1; IL-2: interleukin 2; IL-6: interleukin 6; LN: lupus nephritis; SLE: systemic lupus erythematosus; SRI-4: Systemic Lupus Erythematosus Responder Index 4.